No significant differences among three approaches to antibiotic therapy for community-acquired pneumonia.

Action Points

Empirical treatment for suspected community-acquired pneumonia can be simpler than many guidelines recommend.

Note that beta-lactam antibiotic monotherapy was noninferior to fluoroquinolone monotherapy and to beta-lactam-macrolide combination treatment among patients with CAP who required hospitalization in a non-ICU ward.

Empirical treatment for suspected community-acquired pneumonia (CAP) can be simpler than many guidelines recommend, researchers reported.

In a cluster-randomized, crossover trial, beta-lactam antibiotic monotherapy was noninferior to fluoroquinolone monotherapy and to beta-lactam-macrolide combination treatment, according to Cornelis H. van Werkhoven, MD, of the University Medical Center Utrecht in the Netherlands, and colleagues.

Evidence for such recommendations is limited, Van Werkhoven and colleagues added, but they have led to an increased use of both macrolides and fluoroquinolones, classes associated with increasing microbial resistance.

In the CAP-START trial, they assessed whether patients entering a hospital whose preferred empirical therapy was beta-lactams alone did better or worse than those entering hospitals that preferred one of the other strategies.

For consecutive periods of 4 months, seven Dutch hospitals used beta-lactam monotherapy, beta-lactam with a macrolide, or fluoroquinolone monotherapy as their preferred empirical treatment, switching in an order that was randomly decided at each institution.

For beta-lactams, the preferred empirical treatment was amoxicillin, amoxicillin plus clavulanate, or a third-generation cephalosporin, but penicillin was not allowed.

For beta-lactam-macrolides, the strategy included penicillin, amoxicillin, amoxicillin plus clavulanate, or a third-generation cephalosporin in combination with azithromycin (Zithromax), erythromycin, or clarithromycin (Biaxin).

Patients were eligible if they were over 18 and needed both antibiotic therapy and non-ICU hospital care. Treating physicians were urged to stick with a hospital's preferred strategy for each period but could vary from it for medical reasons in individual cases.

The primary outcome was all-cause mortality within 90 days of admission, while secondary outcomes included time to starting oral treatment, length of stay, and incidence of complications.

Patients weren't randomized individually, the researchers noted, and all of the medications are used in current practice, so individual consent to treatment wasn't regarded as necessary.

However, consent within 72 hours of admission was required for data collection, they reported.

Over the study period from February 2011 to August 2013, 3,325 patients were eligible for the study, and 2,283 gave consent. Of those, 656 got beta-lactams alone, 739 got beta-lactams with a macrolide, and 888 got a fluoroquinolone.

The study was designed to test noninferiority of beta-lactam monotherapy to either of the other two strategies, with a noninferiority margin of 3 percentage points and 90% two-sided confidence interval.

The crude 90-day mortality was 9.0% for beta-lactam monotherapy, 11.1% for beta-lactam/macrolides, and 8.8% for fluoroquinolones, Van Werkhoven and colleagues reported.

In an intent-to-treat analysis, patients receiving beta-lactams with a macrolide had a risk of death that was 1.9 percentage points higher than those receiving beta-lactams alone, they found.

On the other hand, the mortality risk for patients getting fluoroquinolones was lower by 0.6 percentage points than it was among those getting the beta-lactam strategy.

Results were similar when the analysis was confined to patients with radiologically-confirmed CAP, they found.

For all strategies, the median length of stay was 6 days, with a range of 4 to 8 days for fluoroquinolone and beta-lactam monotherapy and a range of 4 to 10 days for beta-lactam-macrolide combination therapy.

There were no significant differences in the incidence of major or minor complications, the researchers reported.

The findings should have wide application, the researchers noted, because all patients for whom any of the strategies might have been used in daily practice were eligible.

On the other hand, regional variations in the prevalence of various cause of CAP might tend to reduce generalizability, they said.

In particular, they noted, "higher incidences [than are seen in the Netherlands] of community-acquired Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus (MRSA) infections would require the adaptation of all three treatment strategies."

The stody was supported by the Netherlands Organization for Health Research and Development.

van Werkhoven and co-authors disclosed no relevant relationships with industry.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.